American cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis resistant to meglumine antimoniate, but with good response to pentamidine: a case report

This is a case report of a Brazilian soldier with cutaneous leishmaniasis. The lesion relapsed following two systemic treatments with meglumine antimoniate. The patient was treated with amphotericin B, which was interrupted due to poor tolerance. Following isolation of Leishmania sp., six intralesional infiltrations of meglumine antimoniate resulted in no response. Leishmania sp promastigotes were again isolated. The patient was submitted to intramuscular 4mg/kg pentamidine. Parasites from the first and second biopsies were identified as Leishmania (Viannia) braziliensis; those isolated from the first biopsy were more sensitive to meglumine antimoniate in vitro than those isolated from the second biopsy. No relapse was observed.

Slow clinical improvement after treatment initiation in Leishmania/HIV coinfected patients

INTRODUCTION: In Brazil there is a large area of overlap of visceral leishmaniasis (VL) and HIV infection, which favored a increased incidence of coinfection Leishmania/HIV. METHODS: This study evaluated 65 consecutive patients with VL and their clinical response to treatment in two health care settings in Belo Horizonte, Brazil. RESULTS: At baseline, the clinical picture was similar between both groups, although diarrhea and peripheral lymphadenomegaly were more frequent in HIV-infected subjects. HIV-positive patients had lower median blood lymphocyte counts (686/mm³ versus 948/mm³p = 0.004) and lower values of alanine aminotransferase (ALT) (48IU/L versus 75.6IU/L p = 0.016) than HIV-negative patients. HIV-positive status (hazard ratio = 0.423, p = 0.023) and anemia (HR = 0.205, p = 0.002) were independent negative predictors of complete clinical response following antileishmanial treatment initiation. CONCLUSIONS: This study reinforces that all patients with VL should be tested for HIV infection, regardless of their clinical picture. This practice would allow early recognition of coinfection with initiation of antiretroviral therapy and, possibly, reduction in treatment failure.

Oral coinfection can stress peripheral lymphocyte to inflammatory activity in leprosy

INTRODUCTION: This study evaluated the intracellular profile of interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-10 (IL-10) and interferon-γ (IFN-γ) in peripheral blood mononuclear cells (PBMCs) from leprosy patients based on oral infections presence to determine whether these coinfections could be associated with pro-inflammatory activity in leprosy. METHODS: Leprosy patients regardless of clinical form and specific leprosy treatment (n=38) were divided into two groups: Group I - leprosy patients with oral infections (n=19), and Group II - leprosy patients without oral infections (n=19). Non-leprosy patients presenting oral infections were assigned to the control Group (n=10). Intracellular IL-2, IL-4, IL-10 and IFN-γ production was evaluated by flow cytometry (FACS) before and 7 days after controlling the oral infection in the Group I, before and 7 days after dental prophylaxis in the Group II, and during oral infection process in control Group. RESULTS: Low percentages of CD3+ lymphocytes bearing IL-2, IL-10 and IFN-γ were observed in the Group I and Group II at baseline and 7 days after therapy or prophylaxis compared to controls. Group I showed reduced percentages of IL-4 at baseline and 7 days after therapy compared to controls, or at baseline of Group II, and the Group II showed reduced percentages of CD3+ cells bearing IL-4 compared to control. An increase of the percentages of CD3+cells bearing IL-4 was observed in the Group I after the oral infections treatment. CONCLUSIONS: The occurrence of oral infections favors the intracellular cytokines expression and, probably, the inflammatory reaction operating as a stimulatory signal triggering the leprosy reactions.

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

^a Introduction Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. Methods This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. Results In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. Conclusions The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

Poor response to azithromycin in cutaneous leishmaniasis leading to a premature interruption of a multicentric phase III clinical trial in Brazil

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions Azithromycin is ineffective for CL treatment and does not seem to have a role in the therapeutic arsenal for CL.

Risk-benefit assessment of Bacillus Calmette-Guérin vaccination, anti-phenolic glycolipid I serology, and Mitsuda test response: 10-year follow-up of household contacts of leprosy patients

Abstract: INTRODUCTION: Despite multidrug therapy, leprosy remains a public health issue. The intradermal Bacillus Calmette-Guérin (BCG) vaccine, Mitsuda test (lepromin skin test), and anti-phenolic glycolipid I (PGL-I) serology are widely used in leprosy studies and have shown great epidemiological value. METHODS: This longitudinal study evaluated the relative risks and benefits of these three tools by comparing results observed in household contacts (HHCs) of leprosy patients who developed leprosy with those of HHCs who did not in a population of 2,992 individuals monitored during a 10-year period. RESULTS : Seventy-five (2.5%) new leprosy cases were diagnosed, including 28 (0.9%) co-prevalent cases. Therefore, for the risk-benefit assessment, 47 (1.6%) HHCs were considered as truly diagnosed during follow-up. The comparison between healthy and affected contacts demonstrated that not only did BCG vaccination increase protection, but boosters also increased to 95% relative risk (RR) reduction when results for having two or more scars were compared with having no scars [RR, 0.0459; 95% confidence interval (CI), 0.006-0.338]. Similarly, Mitsuda reactions >7mm in induration presented 7-fold greater protection against disease development compared to reactions of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, anti-PGL-I ELISA seropositivity indicated a 5-fold RR increase for disease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combined effect of no BCG scars, Mitsuda reaction of <7mm, and seropositivity to anti-PGL-I increased the risk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoption of these combined assays may impose measures for leprosy control strategies.

Changes in the floristic composition of a Terra Firme rain forest In Brazilian Amazonia over an eight-year period In response to logging

Changes in the floristic composition over an eight-year period in a logged area at the Tapajós National Forest in Brazilian Amazonia arc discussed. Two treatments of different intensities of logging were compared with an undisturbed (control) forest. Data were collected from permanent sample-plots. The effects of logging on floristic composition were stronger in the more heavily logged treatment. The number of species decreased immediately after logging, but started to increase before the fifth year after logging and was higher at the end of the study period than before logging. The more heavily logged plots responded more to disturbances, as judged by the increase in the number of species during the period after logging. This forest appears to recover its initial floristic composition after disturbance without intervention.

Growth rate of a terra firme rain forest in Brazilian Amazonia over an eight-year period in response to logging

This paper deals with growth rates of trees > 5cm dbh over an eight-year period from 257 species at the Tapajós National Forest. The discussion is centred on the behaviour of the forest after logging. Permanent sample plots were established in 1981 and measured at the first time. The area was logged in 1982. Measurements after logging occurred in 1983, 1987 and 1989. Considering all species together, diameter increment was similar for both intensities of logging until five years after logging. Light-demanding species showed significantly higher growth rates than shade-tolerant species in the logged forest, with greater increment in the heavier treatment intensity. Commercial species also had higher growth rates in the heavier logged area, although those were significantly different only in the period from one to five years after logging. In the undisturbed forest, growth rates increased with increasing dbh size. At species level, growth rate varied between and within treatments, as well as between trees within species, depending mainly on degree of canopy opening. The logging favoured the growth of commercial species, chiefly the light-demanders. Therefore, if the same growth conditions continue being given, for example by silvicultural treatments, to those species of commercial interest, the forest would reach a stock available for harvesting around year 30 after logging. However, the high variation in increment rates indicates that an eight-year period is not sufficient to allow predictions on cutting cycles or polycyclic management systems for the study forest.

Effects of clove oil on the stress response of matrinxã (Brycon cephalus) subjected to transport

Fish transport is one of the most stressful procedures in aquaculture facilities. The present work evaluated the stress response of matrinxã to transportation procedures, and the use of clove oil as an alternative to reduce the stress response to transport in matrinxã (Brycon cephalus). Clove oil solutions were tested in concentrations of 0, 1, 5 and 10 mg/L during matrinxã transportation in plastic bags, supplied with water and oxygen as the usual field procedures in Brazil. Clove oil reduced some of the physiological stress responses (plasma cortisol, glucose and ions) that we measured. The high energetic cost to matrinxã cope with the transport stress was clear by the decrease of liver glycogen after transport. Our results suggest that clove oil (5 mg/l) can mitigate the stress response in matrinxã subjected to transport.

Photosynthetic parameters and growth in seedlings of Bertholletia excelsa and Carapa guianensis in response to pre-acclimation to full sunlight and mild water stress

Light and water are important factors that may limit the growth and development of higher plants. The aim of this study was to evaluate photosynthetic parameters and growth in seedlings of Bertholletia excelsa and Carapa guianensis in response to pre-acclimation to full sunlight and mild water stress. I used six independent pre-acclimation treatments (0, 90 (11h15-12h45), 180 (10h30-13h30), 360 (09h00-15h00), 540 (07h30-16h30) and 720 min (06h00-18h00)) varying the time of exposure to full sunlight (PFS) during 30 days, followed by whole-day outdoor exposure for 120 days. Before PFS, the plants were kept in a greenhouse at low light levels (0.8 mol m-2 day-1). The PFS of 0 min corresponded to plants constantly kept under greenhouse conditions. From the beginning to the end of the experiment, each PFS treatment was submitted to two water regimes: moderate water stress (MWS, pre-dawn leaf water potential (ΨL) of -500 to -700 kPa) and without water stress (WWS, ΨL of -300 kPa, soil kept at field capacity). Plants under MWS received only a fraction of the amount of water applied to the well-watered ones. At the end of the 120-day-period under outdoor conditions, I evaluated light saturated photosynthesis (Amax), stomatal conductance (g s), transpiration (E) and plant growth. Both Amax and g s were higher for all plants under the PFS treatment. Stem diameter growth rate and Amax were higher for C. guianensis subjected to MWS than in well-watered plants. The contrary was true for B. excelsa. The growth of seedlings was enhanced by exposure to full sunlight for 180 minutes in both species. However, plants of B. excelsa were sensitive to moderate water stress. The higher photosynthetic rates and faster growth of C. guianensis under full sun and moderate water stress make this species a promissory candidate to be tested in reforestation programs.

Assessing treatment response to prophylactic lithium use in patients with bipolar disorder

ABSTRACT Objetive To identify potential clinical and epidemiological predictors of long-term response to lithium treatment. Methods A total of 40 adult outpatients followed in an university hospital, with confirmed diagnosis of bipolar disorder and with history of lithium use for at least a six months period, had their response to this medication assessed through the use of a standardized instrument. The ALDA scale is based on retrospective clinical data, in our study assessed through a thoroughly reviewed of the medical charts, and is used to evaluate the clinical improvement with the treatment (Criterion A), corrected by the acknowledgement of possible confounding factors, such as duration of the treatment, compliance and concomitant use of additional medications (Criterion B), in order to estimate the response that can be specifically attributable to lithium. Results Our study found an inverse relation between the number of mood episodes with psychotic symptoms and lithium treatment outcome. Conclusion The results reinforce the hypothesis that lithium seems to be less efficacious in patients with bipolar disorder who present psychotic symptoms.

Ventricular evoked response in patients with hypertrophic obstructive cardiomyopathy treated with DDD pacing

OBJECTIVE: To assess the changes in ventricular evoked responses (VER) produced by the decrease in left ventricular outflow tract gradient (LVOTG) in patients with hypertrophic obstructive cardiomyopathy (HOCM) treated with dual-chamber (DDD) pacing. METHODS: A pulse generator Physios CTM (Biotronik, Germany) was implanted in 9 patients with severe drug-refractory HOCM. After implantation, the following conditions were assessed: 1) Baseline evaluation: different AV delay (ranging from 150ms to 50 ms) were sequentially programmed during 5 to 10 minutes, and the LVOTG (as determined by Doppler echocardiography) and VER recorded; 2) standard evaluation, when the best AV delay (resulting in the lowest LVOTG) programmed at the initial evaluation was maintained so that its effect on VER and LVOTG could be assessed during each chronic pacing evaluation. RESULTS: LVOTG decreased after DDD pacing, with a mean value of 59 ± 24 mmHg after dual chamber pacemaker, which was significantly less than the gradient before pacing (98 + 22mmHg). An AV delay >100ms produced a significantly lower decrease in VER depolarization duration (VER DD) when compared to an AV delay <=100ms. Linear regression analyses showed a significant correlation between the LVOTG values and the magnitude of VER (r=0.69; p<0.05) in the 9 studied patients. CONCLUSION: The telemetry obtained intramyocardial electrogram is a sensitive means to assess left ventricular dynamics in patients with HOCM treated with DDD pacing.

Response of blood pressure to maximum exercise in hypertensive patients under different therapeutic programs

OBJECTIVE: To evaluate the behavior of blood pressure during exercise in patients with hypertension controlled by frontline antihypertension drugs. METHODS: From 979ergometric tests we retrospectively selected 49 hipertensive patients (19 males). The age was 53±12 years old and normal range rest arterial pressure (<=140/90 mmHg) all on pharmacological monotherapy. There were 12 on beta blockers; 14 on calcium antagonists, 13 on diuretics and 10 on angiotensin converting enzyme inhibitor. Abnormal exercise behhavior of blood pressure was diagnosed if anyone of the following criteria was detected: peak systolic pressure above 220 mmHg, raising of systolic pressure > or = 10 mmHg/MET; or increase of diastolic pressure greater than 15 mmHg. RESULTS: Physiologic response of arterial blood pressure occurred in 50% of patients on beta blockers, the best one (p<0.05), in 36% and 31% on calcium antagonists and on diuretics, respectively, and in 20% on angiotensin converting enzyme inhibitor, the later the leastr one (p<0.05). CONCLUSION: Beta-blockers were more effective than calcium antagonists, diuretics and angiotensin-converting enzyme inhibitors in controlling blood pressure during exercise, and angiotensin converting enzyme inhibitors the least effective drugs.

Immunologic evaluation in infective endocarditis

OBJECTIVE: To analyze the immune response in peripheral blood of patients with infective endocarditis. METHODS: We studied 10 patients with infective endocarditis, age range from 20 to 50 years-old, males and females, and 20 healthy subjects in the same age range. The diagnosis of the disease was based on the clinical picture, echocardiogram, and hemoculture based upon samples drawn and tested before the treatment started. The were no history of atopy or malnutrition, no autoimmune disease, and they were not using any immunosuppressant or antibiotic medication. RESULTS: The patients with endocarditis had significantly higher T and B lymphocyte, CD4+ and CD8+ cell counts, IgM and IgG serum levels, and C4 component of the complement than the control group; no significant difference concerning serum IgA and neutrophil oxidative metabolism; a significant decrease in C3, chemotaxis, and monocyte phagocytosis;cryoglobulins were detected in 66.6% of patients and they were formed by IgG, IgM, IgA, C3, and C4. CONCLUSION: The patients with infective endocarditis were immunocompetent in most sectors of immune response and, at a certain moment, an autoimmune component may be present.